Chronological Change of Vascular Reactivity to cGMP Generators in the Balloon-Injured Rat Carotid Artery

J Vasc Res. 2019;56(3):109-116. doi: 10.1159/000498896. Epub 2019 May 14.

Abstract

Background/aims: Soluble guanylate cyclase (sGC) exists as reduced, oxidized, and heme-free forms. Currently, it is unclear whether endovascular mechanical stenosis has an impact on vascular tone control by drugs targeting sGC, namely cGMP generators.

Methods: Pharmacological responses to acidified sodium nitrite (reduced sGC stimulant) and BAY 60-2770 (oxidized/heme-free sGC stimulant) were studied in balloon-injured rat carotid arteries at several time points. In addition, sGC expression was detected by immunohistochemistry.

Results: At 1 day after injury, acidified sodium nitrite-induced relaxation was attenuated in the injured artery, whereas BAY 60-2770-induced relaxation was augmented. Similar attenuation of response to acidified sodium nitrite was seen at 7 and 14 days after injury. On the other hand, the augmentation of response to BAY 60-2770 disappeared at 7 and 14 days after injury. At 1 day after injury, the immunohistochemical expression pattern of sGC in the smooth muscle layer of the injured artery was not different from that of the uninjured artery. However, in the injured artery, the intensity of sGC staining was weak at 7 and 14 days after injury.

Conclusion: Balloon injury alters vascular responsiveness to cGMP generators, which seems to be associated with the form and/or expression of sGC.

Keywords: Balloon injury; Nitric oxide; Redox state; Soluble guanylate cyclase; Vascular reactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon
  • Animals
  • Benzoates / pharmacology*
  • Biphenyl Compounds / pharmacology*
  • Carotid Arteries / drug effects
  • Carotid Arteries / enzymology
  • Carotid Arteries / pathology
  • Carotid Artery Injuries / drug therapy*
  • Carotid Artery Injuries / enzymology
  • Carotid Artery Injuries / pathology
  • Cyclic GMP / metabolism*
  • Disease Models, Animal
  • Enzyme Activation
  • Enzyme Activators / pharmacology*
  • Hydrocarbons, Fluorinated / pharmacology*
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / enzymology
  • Muscle, Smooth, Vascular / pathology
  • Nitric Oxide Donors / pharmacology*
  • Rats, Sprague-Dawley
  • Second Messenger Systems
  • Sodium Nitrite / pharmacology*
  • Soluble Guanylyl Cyclase / metabolism*
  • Time Factors
  • Vasodilation / drug effects*

Substances

  • 4-(((4-carboxybutyl) (2- (5-fluoro-2-((4'-(trifluoromethyl) biphenyl-4-yl)methoxy)phenyl)ethyl) amino)methyl)benzoic acid
  • Benzoates
  • Biphenyl Compounds
  • Enzyme Activators
  • Hydrocarbons, Fluorinated
  • Nitric Oxide Donors
  • Soluble Guanylyl Cyclase
  • Cyclic GMP
  • Sodium Nitrite